Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size.
Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size.
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DOI：
10.1016/j.celrep.2021.109644
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发表时间：
2021-08-31
期刊：
影响因子：
8.8
通讯作者：
O'Connor MB
中科院分区：
文献类型：
--
作者：
Pan X;O'Connor MB
在全变态昆虫中，变态时间和身体大小由产生蜕皮激素的前胸腺（PG）和产生PTTH的突触前神经元（PGNs）组成的神经内分泌轴控制。虽然PTTH/躯干信号被认为是变形时间的主要介质，但最近的研究表明，其他未识别的PGN衍生因素也会影响时间。在这里，我们证明了受体酪氨酸激酶间变性淋巴瘤激酶（Alk）和PDGF和VEGF受体相关（Pvr）与PTTH/躯干信号协调作用，以调节蛹化时间和身体大小。Alk和Pvr均触发PG中的Ras/Erk信号以上调蜕皮激素生物合成酶的表达，而Alk还通过激活磷脂酰肌醇3-激酶（PI 3 K）/Akt来抑制自噬。Alk配体Jelly belly（Jeb）由PGN产生并作为第二PGN衍生的向性因子，而Pvr活化主要依赖于PG衍生的Pvf 2和Pvf 3的自分泌信号传导。这些发现表明，阿曲他克林和自分泌信号的组合调节变态的时间，定义事件的全代谢发展。Pan和奥康纳将Jeb/Alk和Pvf/Pvr识别为控制果蝇发育时间和身体大小的额外信号通路。Jeb/Alk信号传导在前胸腺（PG）神经元和PG之间以外分泌方式发生以控制蜕皮激素产生，而Pvf/Pvr信号传导通过PG自身内的自分泌活性。
In holometabolous insects, metamorphic timing and body size are controlled by a neuroendocrine axis composed of the ecdysone-producing prothoracic gland (PG) and its presynaptic neurons (PGNs) producing PTTH. Although PTTH/Torso signaling is considered the primary mediator of metamorphic timing, recent studies indicate that other unidentified PGN-derived factors also affect timing. Here, we demonstrate that the receptor tyrosine kinases anaplastic lymphoma kinase (Alk) and PDGF and VEGF receptor-related (Pvr), function in coordination with PTTH/Torso signaling to regulate pupariation timing and body size. Both Alk and Pvr trigger Ras/Erk signaling in the PG to upregulate expression of ecdysone biosynthetic enzymes, while Alk also suppresses autophagy by activating phosphatidylinositol 3-kinase (PI3K)/Akt. The Alk ligand Jelly belly (Jeb) is produced by the PGNs and serves as a second PGN-derived tropic factor, while Pvr activation mainly relies on autocrine signaling by PG-derived Pvf2 and Pvf3. These findings illustrate that a combination of juxtacrine and autocrine signaling regulates metamorphic timing, the defining event of holometabolous development. Pan and O’Connor identify Jeb/Alk and Pvf/Pvr as additional signaling pathways that control developmental timing and body size in Drosophila. Jeb/Alk signaling occurs in a juxtracrine fashion between the prothoracic gland (PG) neurons and the PG to control ecdysone production, while Pvf/Pvr signals via autocrine activity within the PG itself.
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